Synthesis and Enzymatic Evaluation of a Small Library of Substituted Phenylsulfonamido-Alkyl Sulfamates towards Carbonic Anhydrase II.

A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, -, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates -, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds - showed no inhibition of the enzyme, in contrast to sulfamates -. Thus, the inhibitory potential of compounds - towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the position proved to be better for inhibiting CAII than compounds with the same substituent in the or position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as K = 0.67 μM (for ) and a -butyl substituent in position and acted as a competitive inhibitor of the enzyme.